Steroidogenic Isoenzymes in Human Hair and Their Potential Role in Androgenetic Alopecia

Abstract

Androgenetic alopecia (AGA) is the most common type of hair loss. The relatively strong concordance of the degree of baldness in fathers and sons is not consistent with a simple Mendelian trait, and a polygenic basis is considered to be most likely. So far, the predisposing genes for AGA are unknown and we do not understand the molecular steps involved in androgen-dependent beard growth versus androgen-dependent hair loss, but AGA can be defined as a dihydrotestosterone (DHT)-dependent process with continuous miniaturization of sensitive hair follicles. The type 2 5α-reductase plays a central role by the intrafollicular conversion of testosterone to DHT. However, due to the increasing knowledge in this field, we now know that there are many more steroidogenic enzymes involved in the onset and development of AGA, and this article shall provide a critical overview of recent discoveries.

The human skin as a hormone target and an endocrine gland

“…They also express P450 side chain cleavage enzyme which catalyses the conversion of cholesterol into pregnenolone, cytochrome P450 17-hydroxylase that leads to precursors of cortisol and DHEA, and steroidogenic factor-1 which maintains these reactions. DHEA can be further converted into androstenedione and the tissue potent androgen testosterone by sebocytes and dermal papilla cells since they express 3â-hydroxysteroid dehydrogenase-Ä 5-4 isomerase 3,156,157 . Further activation of testosterone by its conversion into 5á-DHT is catalyzed by 5á-reductase type 1 which is expressed in almost all skin cells but especially in sebocytes 81 , while fibroblasts and dermal papilla cells also express 5á-reductase type 2 37 .…”

“…Androgen conversion to estrogens in the skin takes place in dermal fibroblasts which express the responsible enzyme cytochrome P450 19 (aromatase), and androgen inactivation to androsterone or 3á-androstanediol in epidermal keratinocytes which strongly express the responsible enzyme 3á-hydroxysteroid dehydrogenase 3,158 . In contrast to this skin-related pathway, conversion of the adrenal DHEA sulfate -which reaches the skin through the circulation -to DHEA occurs with the assistance of dermal papilla cells and monocytes which exhibit steroid sulfatase activity 156,157,159 . Therefore, the skin is a steroidogenic tissue and different skin cell types exert distinct duties in the synthesis of tissue active androgens and their inactivation leading to androgen and estrogen homeostasis.…”

Trace elements content and hormonal profiles in women with androgenetic alopecia

“…Androgenic alopecia (AGA) is one of the common types of hair loss in women that is intesifying with age [1,2]. AGA is the complicated and combined result of an androgen-dependent process based on genetic susceptibility of the androgen receptors (AR) to androgens and intrafollicular conversion of weak androgens to potentially stronger ones via numerous steroid-converting enzymes.…”

Expression of Sex-Determining Genes in the Scalp of Men with Androgenetic Alopecia

“…Androgenetic alopecia (AGA) can be defined as a 5α-dihydrotestosterone-mediated process with continuous miniaturization of androgen-sensitive hair follicles [1]. Since most affected individuals, especially men, exhibit normal circulating levels of androgens, the intrafollicular conversion of testosterone to 5α-dihydrotestosterone seems to play a central role in the induction of androgenetic hair loss.…”